In patients with reduced or lost renal function waste products of the natural metabolism including uremic toxins are removed by means of renal replacement therapy or dialysis method. Thereby the removal of substances from the blood, which is taken from the patient and is led extracorporeal, is performed by contact of the blood with a dialysate, wherein blood and dialysate contact with each other not directly, but through a membrane. The dialysate is mixed with various salts and thus calls forth diffusive and convective effects which are responsible for the transport of substances from the blood into the dialysate via the extracorporeal arranged membrane. After performed removal of a portion of the waste substances the so treated blood is fed back to the patient.
For the test of a dialysis apparatus, parts of a dialysis apparatus or changed dialysis parameters, the concentrations of uremic toxin will be determined before and after a dialysis therapy. The reduction of the respective substances represents the central basis for the assessment of dialysis dose.
A common marker element is carbamide which is also known as urea. Accordingly, the urea reduction rate is regarded as a critical parameter in the dialysis technique. The determination of the urea reduction can be carried out in different ways.
A classical method represents the chemical determination of the urea concentration in the blood before and after a dialysis therapy. The problem of this method is, however, that the blood sample must be taken from the patient and be sent to a laboratory which is equipped for the determination of the urea concentration. This process can take quite several days.
Furthermore, the urea concentration or its change by the determination of the conductivity in the dialysate can be determined. A product on the market that works according to this principle is the product Biostat© Urea Monitor of the company Baxter. The problem during the measurement with conductivity is that conductivity change can be effected by other influence factors, e.g. by pH changes and that thus the measurement is distorted in circumstances.
A third possibility for determining the dialysis dose is the measurement of uric acid reduction which—as is generally known—corresponds substantially to the urea reduction, through a dialysis therapy by means of UV absorption measurements in the outflow of the dialysate. Uhlin has shown in his dissertation on the topic “Haemodialysis Treatment monitored on-line by ultra violet absorbance” [Linköping University Medical Dissertation No 962, 2006] that the absorption change in the outflowing dialysate at 280 nm represents a very good correlation to the concentration change of urea in the blood of the patient. Such a measuring device is described in EP 1 083 948 B1. In this prior art, both the configuration and the position of the sensor for dialysis technical applications is described.
Most of all, it is not possible with the apparatuses and methods known from the prior art to provide promptly on or during the therapy of the patient a differentiation of other waste substances or toxic substances of urea preferably simultaneously or at the same time.
DE 2934190 A1 discloses a method for molecular spectroscopy, in particular for the determination of metabolic products, in which the absorption of infrared radiation is measured though a sample containing a substance to be determined. As most preferred substance to be determined glucose is known. Thereby, the glucose determination is carried out in the whole blood or serum or in the urine with Raman lasers or carbon dioxide (CO2) lasers as light source. DE 2934190 A1 describes that the concentration of several substances can be measured, wherein several wavelengths must be radiated simultaneously though the sample. In addition, DE 2934190 A1 points out the possibilities for developing an extracorporeal or also implantable artificial pancreas. The method described in DE 2934190 A1 shows the person skilled in the art that it is in principle possible to determine by means of infrared spectroscopy several substances simultaneously, i.e. their presence and allegedly, also their concentrations. This method is however unsuitable to measure blood samples or blood serum samples. Furthermore, the substances to be determined in the blood or dialysate flow indicate no clearly differentiable infrared spectrums. The substances measured in DE 2934190 A1 are well suitable to be determined by means of infrared. Due to the significantly different substance properties which are determined by means of infrared and UV, the measuring arrangement described in DE 2934190 A1 and the measuring methods cannot be applied to the UV range. In the UV range the absorption of the whole molecule, which is associated with the concentration of a substance, is determined, while certain types of bonds in a molecule are excited by means of IR and thus IR mainly is used to prove the presence of certain functional groups. The IR-measuring device described in DE 2934190 A1 cannot be simply replaced by a UV-measuring device or by a NMR-measuring device, because they are fundamentally different techniques, which are not equivalent interchangeable.
DE 69916053 T2 relates to a method for determining waste products in the dialysate during dialysis treatments. The method is for the exact determination of the amount of waste products in the dialysate during the dialysis treatment as well as for measuring urea or any other substance contained in the waste products. Thus, the determination can be optionally applied by measuring the substances which are most suitable for the selection of the dialyzer and the control of the dialysis machine in order to adjust the dialysis treatment to the patient. DE 69916053 T2 gives no evidence for the use of light emitting diodes (LEDs) and dispenses with a reference substance. Furthermore, DE 69916053 T2 gives the person skilled in the art no evidence, how several or all UV-active substances in the blood or the dialysate outflow can be determined quantitatively.
U.S. Pat. No. 5,772,606 discloses a urinal with a measuring system, with which the amounts of uric components, glucose, hemoglobin, albumin, lithium acetacetate, ascorbic acid, creatinine, sodium chloride and sodium nitrite can be determined. The measuring system disclosed in U.S. Pat. No. 5,772,606 uses the wavelength range between 400 and 2500 nm. As light source lasers are disclosed.
JP 02027264 A describes the measurement of proteins in the urine at a wavelength of 610 nm. As light source light emitting diodes (LED) are used. Proteins absorb, however also in the UV range below 210 nm and at 280 nm. However, the absorption at 280 nanometers requires the presence of the amino acids tryptophan and tyrosine in the amino acid sequence because other amino acids do not absorb in the UV range, wherein disulfide bonds and phenylalanine influence the UV absorption minimal. Below 210 nm absorb the peptide bonds in a protein. Due to the commonness of the peptide bonds in a protein, it is a very sensitive area of the protein spectrum. So a quantitative protein determination in sample liquids is possible, but using the obtained spectrum without knowledge of the respective extinction coefficient the proteins contained cannot be identified. Also with the apparatus disclosed in JP 02027264 A and the method, the determination of uremic toxins is not possible. The determination in the infrared range has the disadvantage that the sample to be measured is heated by the infrared radiation passing the sample. This can lead to rearrangement or degradation of the uremic toxins to be measured and to a change of the extinction coefficient so that with the inventive apparatus for extracorporeal blood treatment for differentiation of uremic toxins in the outflow of the apparatus the uremic toxins in the outflow of the apparatus can be no longer differentiated. Infrared measurements investigate other substance properties than UV measurements. The measuring methods are therefore to be considered substance-specific, as other optical properties are required. Thus, it is not possible with the experimental configuration described in JP 02027264 A to determine several or all UV active substances in the blood or the dialysate outflow. As above indicated, IR spectroscopy and UV spectroscopy are directed to clearly different molecular properties and both methods cannot be replaced equivalent.